Cancers of digestive system account for greater than 18% of cancers; out of 274,000 diagnosed, greater than 130,000 die per year. 43,140 men and women were diagnosed with and 36,800 died of cancer of the pancreas in 2010.
Pancreatic cancer is often a fatal disease with 5-year survival rates of only 1% to 4%. Early detection can substantially reduce the mortality rate. Simple, non-invasive screening tests are urgently needed to improve the current low survival rate of cancer patients.
There are several high-risk factors for pancreatic cancer, including family history, smoking, diabetes and obesity. These groups are primary candidates for pancreatic cancer screening. Mutations of the KRAS2 (also known as v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog) oncogene (such as in codon 12) are present in approximately 90% to 95% of cases of pancreatic cancer. Despite the fact that KRAS mutations are not entirely specific to pancreatic cancer, the early detection of these mutations in high-risk individuals can save lives.
At the early stages of the cancer disease, cancerous cells and DNA are shed into the duodenum along with the pancreatic secretions. In the same fashion, biomarkers from stomach, esophagus, gall bladder and liver are shed into the GI tract. Serum biomarkers such as circulating tumor cells and circulating DNA appear relatively later in the disease.
Pancreatic secretions can be obtained endoscopically, but the procedure causes significant discomfort and cannot be used for routine screening. Stool is another source of gastrointestinal cancer-derived DNA that can be used for early screening. However, the sensitivity of detection of pancreatic cancer in stool is relatively low. The hostile environment of the gastrointestinal tract composed of bile salts, DNases, and bacteria reduces the chances that pancreatic cancer-derived DNA will survive during the passage.
Current early diagnostic methods of cancer include: endoscopic ultrasound, which are sensitive, but expensive and not for screening, and endoscopy is invasive; imaging (CT, MRI), which are expensive and cannot be used screening; and, blood testing for carbohydrate antigen 19-9, also called cancer antigen 19-9, or CA19-9, which gives a large proportion of false negatives and false positives.
For stomach and esophageal cancers, no screening procedure is available besides endoscopy. However, this is a costly procedure and is usually performed only in high risk populations such as in Japan.